The overall objective of this proposal is to investigate the hypothesis that dietary levels of phytoestrogens are neuroprotective to the aging central nervous system (CNS). Perimenopausal women are encouraged to increase their intake of phytoestrogens (found in soy) as an alternative to synthetic hormone replacement therapy. Evidence suggests that phytoestrogens can protect against osteoporosis and cardiovascular disease, but little is known about what CNS effects they may have. Endogenous and synthetic estrogens have been found to affect brain morphology (e.g., dendritic spine density) and gene transcription (e.g., estrogen receptor mRNA), provide resistance to brain damage from ischemic events, and enhance cognitive performance. Phytoestrogens bind the estrogen receptors (ERalpha and ERbeta), and at dietary levels may have neuroprotective actions similar to 17beta estradiol (E2) on the CNS. For this proposal, effects of phytoestrogens on brain regions involved in cognitive function are of particular interest. Using an aging rodent model, 2 specific aims will be addressed in small, self-contained research projects: 1) assessment of cognitive effects of dietary phytoestrogens; 2) assessment of the neuroprotective role of dietary phytoestrogens in a rodent model of ischemic stroke. For specific aim 1, end points include acquisition and performance of memory-intensive tasks, as well as neuroanatomical and neurochemical measures after intake of diets made of soy protein with or without phytoestrogens. For specific aim 2, end points include morphological measures (size of infarct) and number of cells with ischemia-induced damage in regions surrounding the infarct.